Caffeine helps premature babies breathe a little easier…but how much and for how long?

The caffeine in coffee might help get you going in the morning, but for premature babies it can be lifesaving. For more than a decade neonatologists have routinely given premature newborns caffeine as a respiratory stimulant, helping their immature lungs and brains remember to breathe and reducing episodes of intermittent hypoxia (IH)—short, repetitive drops in blood oxygen levels.

Typically, babies are weaned off caffeine once they’re developmentally mature enough to breathe normally without help, usually around 34 weeks’ gestational age. “It’s at about that age that most babies stop having clinically obvious hypoxic spells,” explains Boston Children’s Hospital pulmonologist and neonatologist Lawrence Rhein, MD. “But the question has been, are there continued but less obvious episodes that we could and should be preventing? And can caffeine play a role in doing so?”

It’s an important question to ask. While no single IH episode has much effect, lack of oxygen over days or weeks can affect a baby’s lungs, brain and heart, and fuel inflammation within her tissues and organs—all of which can have long-term developmental impact.

Rhein and colleagues from 15 other hospitals across the U.S.—together comprising the Caffeine Pilot Study Group—came together to probe the question. Their answer: pour the baby another cup.

As they reported in JAMA Pediatrics, the group assigned premature babies—treated in the neonatal intensive care units (NICUs) at their respective hospitals over an 18-month period—to one of two groups. The first group was treated with caffeine as usual, stopping at 34 weeks’ gestational age. The babies in the second group received caffeine for an additional six weeks.

The researchers used continuous pulse oximetry to measure the blood oxygen levels of both groups until all of the babies reached 40 weeks, looking for any differences in the number of IH episodes and the amount of time the babies spent with blood oxygen levels below 90 percent saturation.

It was amazing what a little extra caffeine could do. For babies in the extended treatment group, the number of IH episodes with oxygen saturation below 90 percent dropped by as much as 52 percent, depending on age. And those babies experienced as much as 47 percent less time under 90 percent saturation, again compared to babies given the standard treatment.

“Oxygen desaturation is bad for the brain and increases mortality risk,” Rhein explains. “But several large multicenter trials, including BOOST, SUPPORT and COT, all agreed that babies kept at lower oxygen levels have a lower risk of ROP.”

Rhein thinks caffeine helps strike that balance. “By stimulating the brain and reminding them to breathe, caffeine treatment allows babies to receive the benefits of higher oxygen saturation while reducing the toxic effects of exposure.”

A major question still remains unanswered: Which IH episodes are important enough to treat and which can be ignored—if any?

“Our oximetry data showed that IH episodes can continue for weeks after caffeine is discontinued,” Rhein says. “Those episodes were not clinically obvious, but we don’t yet know which episodes we need to react to. We’re setting the stage to ask whether some of these episodes that we don’t think are significant can affect long-term cognitive development.”

Rhein views the debate about oxygen and premature newborns in a larger context.

“How can we better guide parents about what to do while their child is in the NICU? Can reducing desaturations promote neurocognitive development and relieve some of the need for special education resources for children born prematurely? Can this help reduce the short- and long-term care costs to the health care system? These are all questions we need, and are hopefully now poised, to answer.”